Effect of tensile mechanical stress on the synthesis of metalloproteinases by rabbit coronal sutures in vitro.

The application of a continuous tensile mechanical stress (30 g) to explants of coronal sutures from newborn rabbits (1-2 days) produced increases in enzyme activity of 33.7% for collagenase, 95.2% for gelatinase, and 35.9% for NMP III over a 4-day culture period. All three activities were in latent form and required activation with either 4-APMA or trypsin. The increases in enzyme activities were not accompanied by an alteration in the degradation of structural proteins. This was due to the ability of the cells to synthesize an inhibitor (mol wt 29,000 daltons) which complexed the increased quantities of enzyme. This necessitated a substantial stimulation of inhibitor production because there was still a residue of free inhibitory activity in the media of stressed cultures after 4 days. We previously showed using the same model system that coronal sutures respond to tensile mechanical stress by a two-fold increase in collagen synthesis. The present data suggest that when the priority of the cell population is the synthesis of structural proteins, the inhibitor, in addition to preventing the hydrolysis of newly synthesized peptides, also maintains matrix degradation at normal turnover levels.